804 Fibroblast subpopulations orchestrate chronic inflammation in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by massive immune cell infiltrate, extensive fibrosis, and tissue destruction. We aimed to elucidate the role of fibroblasts in pathophysiology HS. Single-cell RNA-sequencing was performed on chronic lesional samples 6 HS patients 7 controls. Spatial sequencing 4 samples. Fibroblast subclustering revealed subsets (SFRP2+, COL11A+, SFRP4+, LSP1+, RAMP1+, CXCL13+). Two these, SFRP4+ CXCL13+, were specifically derived from displayed enhanced pro-fibrotic characteristics (increased COL1A1 COL3A1 expression). Development activation these found be driven key HS-associated cytokines (IFNγ, IL-1β, TNF). IHC spatial that their location demarcates area skin. Activated CXCL13+ FB shown help coordinate characteristic infiltrate attracting neutrophils Th17 cells through expression chemokines including CXCL5, CXCL6, CCL20. Furthermore, increased CXCL13 subset likely facilitates migration B environment formation tertiary lymphoid structures located within fibrotic zone surrounding infiltrate. These findings demonstrate distinct subsets, activated cytokines, shaping composition architecture